Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer
Abstract Background Pancreatic cancer is a highly lethal malignancy with limited treatment response. Despite advancements in treatment, systemic chemotherapy remains the primary therapeutic approach for over 80% of patients, with no established biomarkers to guide drug selection. Traditional two-dim...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-025-02374-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850223773364518912 |
|---|---|
| author | Jin Su Kim Chan Hee Park Eunyoung Kim Hee Seung Lee Jinyoung Lee Jeehoon Kim Eun Hee Kam Sanghee Nam Moon Jae Chung Jeong Youp Park Seung Woo Park Sangwoo Kim Galam Leem Seungmin Bang |
| author_facet | Jin Su Kim Chan Hee Park Eunyoung Kim Hee Seung Lee Jinyoung Lee Jeehoon Kim Eun Hee Kam Sanghee Nam Moon Jae Chung Jeong Youp Park Seung Woo Park Sangwoo Kim Galam Leem Seungmin Bang |
| author_sort | Jin Su Kim |
| collection | DOAJ |
| description | Abstract Background Pancreatic cancer is a highly lethal malignancy with limited treatment response. Despite advancements in treatment, systemic chemotherapy remains the primary therapeutic approach for over 80% of patients, with no established biomarkers to guide drug selection. Traditional two-dimensional (2D) culture models fail to replicate the tumor microenvironment, necessitating the development of more advanced models, such as three-dimensional (3D) organoid models. Methods We established 3D organoid cultures using patient-derived conditionally reprogrammed cell (CRC) lines, originally cultured under 2D conditions. These CRC organoids were developed using a Matrigel-based platform without organoid-specific medium components to preserve the intrinsic molecular subtypes of the cells. Morphological, molecular, and drug sensitivity analyses were performed to compare the clinical responses of 3D CRC organoids with those of their 2D counterparts and clinical responses. Results The 3D CRC organoids retained the molecular characteristics, transcriptomic and mutational profiles of the parental tumors and displayed distinct morphologies corresponding to cancer stages and differentiation. Drug response profiling of gemcitabine plus nab-paclitaxel (Abraxane) and FOLFIRINOX demonstrated that the 3D organoids more accurately mirrored patient clinical responses than the 2D cultures. Notably, the IC50 values for the 3D organoids were generally higher, reflecting the structural complexity and drug penetration barriers observed in vivo. Conclusion Matrigel-based 3D organoid culture models provide a robust platform for pre-clinical drug evaluation, overcoming the limitations of 2D models. Although time- and resource-intensive, integrating both 2D and 3D platforms enables efficient initial screening and validation. This approach holds promise for identifying predictive biomarkers and advancing precision medicine in pancreatic cancer treatment. |
| format | Article |
| id | doaj-art-ddd7030d47fe4877a9364d06f8d0d564 |
| institution | OA Journals |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj-art-ddd7030d47fe4877a9364d06f8d0d5642025-08-20T02:05:49ZengBMCMolecular Cancer1476-45982025-06-0124111810.1186/s12943-025-02374-yEstablishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancerJin Su Kim0Chan Hee Park1Eunyoung Kim2Hee Seung Lee3Jinyoung Lee4Jeehoon Kim5Eun Hee Kam6Sanghee Nam7Moon Jae Chung8Jeong Youp Park9Seung Woo Park10Sangwoo Kim11Galam Leem12Seungmin Bang13Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDepartment of Biomedical Systems Informatics and Brain Korea 21 Project, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDepartment of Internal Medicine, Graduate School of Yonsei UniversityDepartment of Internal Medicine, Graduate School of Yonsei UniversityDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDepartment of Biomedical Systems Informatics and Brain Korea 21 Project, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineDivision of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of MedicineAbstract Background Pancreatic cancer is a highly lethal malignancy with limited treatment response. Despite advancements in treatment, systemic chemotherapy remains the primary therapeutic approach for over 80% of patients, with no established biomarkers to guide drug selection. Traditional two-dimensional (2D) culture models fail to replicate the tumor microenvironment, necessitating the development of more advanced models, such as three-dimensional (3D) organoid models. Methods We established 3D organoid cultures using patient-derived conditionally reprogrammed cell (CRC) lines, originally cultured under 2D conditions. These CRC organoids were developed using a Matrigel-based platform without organoid-specific medium components to preserve the intrinsic molecular subtypes of the cells. Morphological, molecular, and drug sensitivity analyses were performed to compare the clinical responses of 3D CRC organoids with those of their 2D counterparts and clinical responses. Results The 3D CRC organoids retained the molecular characteristics, transcriptomic and mutational profiles of the parental tumors and displayed distinct morphologies corresponding to cancer stages and differentiation. Drug response profiling of gemcitabine plus nab-paclitaxel (Abraxane) and FOLFIRINOX demonstrated that the 3D organoids more accurately mirrored patient clinical responses than the 2D cultures. Notably, the IC50 values for the 3D organoids were generally higher, reflecting the structural complexity and drug penetration barriers observed in vivo. Conclusion Matrigel-based 3D organoid culture models provide a robust platform for pre-clinical drug evaluation, overcoming the limitations of 2D models. Although time- and resource-intensive, integrating both 2D and 3D platforms enables efficient initial screening and validation. This approach holds promise for identifying predictive biomarkers and advancing precision medicine in pancreatic cancer treatment.https://doi.org/10.1186/s12943-025-02374-yPancreatic cancerConditionally reprogrammed cell (CRC) organoids3D organoid cultureDrug sensitivity screeningPrecision medicineGemcitabine plus nab-paclitaxel (Abraxane) |
| spellingShingle | Jin Su Kim Chan Hee Park Eunyoung Kim Hee Seung Lee Jinyoung Lee Jeehoon Kim Eun Hee Kam Sanghee Nam Moon Jae Chung Jeong Youp Park Seung Woo Park Sangwoo Kim Galam Leem Seungmin Bang Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer Molecular Cancer Pancreatic cancer Conditionally reprogrammed cell (CRC) organoids 3D organoid culture Drug sensitivity screening Precision medicine Gemcitabine plus nab-paclitaxel (Abraxane) |
| title | Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer |
| title_full | Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer |
| title_fullStr | Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer |
| title_full_unstemmed | Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer |
| title_short | Establishing 3D organoid models from patient-derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer |
| title_sort | establishing 3d organoid models from patient derived conditionally reprogrammed cells to bridge preclinical and clinical insights in pancreatic cancer |
| topic | Pancreatic cancer Conditionally reprogrammed cell (CRC) organoids 3D organoid culture Drug sensitivity screening Precision medicine Gemcitabine plus nab-paclitaxel (Abraxane) |
| url | https://doi.org/10.1186/s12943-025-02374-y |
| work_keys_str_mv | AT jinsukim establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT chanheepark establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT eunyoungkim establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT heeseunglee establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT jinyounglee establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT jeehoonkim establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT eunheekam establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT sangheenam establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT moonjaechung establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT jeongyouppark establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT seungwoopark establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT sangwookim establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT galamleem establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer AT seungminbang establishing3dorganoidmodelsfrompatientderivedconditionallyreprogrammedcellstobridgepreclinicalandclinicalinsightsinpancreaticcancer |